5A9E

Cryo-electron tomography and subtomogram averaging of Rous-Sarcoma- Virus deltaMBD virus-like particles

Summary for 5A9E

• Entry DOI: 10.2210/pdb5a9e/pdb
• EMDB information: 3101
• Descriptor: DELTAMBD GAG PROTEIN (1 entity in total)
• Functional Keywords: retrovirus, rous-sarcoma virus, immature retrovirus, virus-like-particle, capsid, viral protein
• Biological source: ROUS SARCOMA VIRUS (RSV)
• Cellular location: Matrix protein p19: Virion . Capsid protein p27: Virion . Nucleocapsid protein p12: Virion : P03322
• Total number of polymer chains: 18
• Total formula weight: 942718.72

Authors

Schur, F.K.M.,Dick, R.A.,Hagen, W.J.H.,Vogt, V.M.,Briggs, J.A.G. (deposition date: 2015-07-21, release date: 2015-08-12, Last modification date: 2024-05-08)

Primary citation

Schur, F.K.M.,Dick, R.A.,Hagen, W.J.H.,Vogt, V.M.,Briggs, J.A.G.
The Structure of Immature-Like Rous Sarcoma Virus Gag Particles Reveals a Structural Role for the P10 Domain in Assembly.
J.Virol., 89:10294-, 2015

PubMed Abstract: The polyprotein Gag is the primary structural component of retroviruses. Gag consists of independently folded domains connected by flexible linkers. Interactions between the conserved capsid (CA) domains of Gag mediate formation of hexameric protein lattices that drive assembly of immature virus particles. Proteolytic cleavage of Gag by the viral protease (PR) is required for maturation of retroviruses from an immature form into an infectious form. Within the assembled Gag lattices of HIV-1 and Mason-Pfizer monkey virus (M-PMV), the C-terminal domain of CA adopts similar quaternary arrangements, while the N-terminal domain of CA is packed in very different manners. Here, we have used cryo-electron tomography and subtomogram averaging to study in vitro-assembled, immature virus-like Rous sarcoma virus (RSV) Gag particles and have determined the structure of CA and the surrounding regions to a resolution of ∼8 Å. We found that the C-terminal domain of RSV CA is arranged similarly to HIV-1 and M-PMV, whereas the N-terminal domain of CA adopts a novel arrangement in which the upstream p10 domain folds back into the CA lattice. In this position the cleavage site between CA and p10 appears to be inaccessible to PR. Below CA, an extended density is consistent with the presence of a six-helix bundle formed by the spacer-peptide region. We have also assessed the affect of lattice assembly on proteolytic processing by exogenous PR. The cleavage between p10 and CA is indeed inhibited in the assembled lattice, a finding consistent with structural regulation of proteolytic maturation.

PubMed: 26223638
DOI: 10.1128/JVI.01502-15

Experimental method

ELECTRON MICROSCOPY (7.7 Å)